Abstract
OBJECTIVES: Bilateral repetitive transcranial magnetic stimulation (brTMS) has shown promise as a therapeutic approach for depression; however, evidence from existing studies remains inconsistent. To address the concern, a meta-analysis was conducted to examine the efficacy and safety of brTMS in comparison with unilateral repetitive transcranial magnetic stimulation (urTMS) or sham repetitive transcranial magnetic stimulation (srTMS) in treating major depressive disorder (MDD) and bipolar depression (BD). METHODS: A systematic search covering publications up to May 22, 2024, was performed across four main bibliographic databases (PubMed, EMBASE, Cochrane Library, and PsycINFO) to identify randomized controlled trials (RCTs) assessing the efficacy and safety of brTMS vs. urTMS or srTMS in patients with MDD or BD. Following Cochrane Handbook guidelines, random-effects meta-analyses were employed to derive pooled estimates for primary and secondary outcomes. RESULTS: The analysis included 20 RCTs (8 comparing brTMS to urTMS, 6 comparing brTMS to srTMS, and 6 comparing brTMS to both urTMS and srTMS), encompassing a total of 1666 participants. No significant difference was observed between brTMS and urTMS regarding study-defined response (9 RCTs, 11 study arms, n = 778; RR 1.20, 95% CI 0.83-1.72; Chi(2) = 29.76, I(2) = 66%; P = 0.34) or study-defined remission (7 RCTs, 8 study arms, n = 684; RR 1.36, 95% CI 0.87-2.12; I(2) = 57%; P = 0.18) in patients with MDD or BD. However, when compared to srTMS, brTMS demonstrated statistically significant improvements in study-defined response (10 RCTs, 12 study arms, n = 595; RR 2.69, 95% CI 1.58-4.57; Chi(2) = 22.75, I(2) = 52%; P = 0.0003) and study-defined remission (8 RCTs, 9 study arms, n = 553; RR 3.84, 95% CI 1.62-9.07; Chi(2) = 14.42, I(2) = 45%; P = 0.002). No significant differences were detected between the brTMS, urTMS, or srTMS groups regarding adverse events or treatment discontinuation rates (P > 0.05). CONCLUSIONS: The meta-analysis indicates that brTMS is an effective, safe, and well-tolerated treatment for MDD and BD but does not provide significant antidepressant advantages over urTMS. Consequently, it actually suggested that brTMS could serve as an alternative treatment strategy in cases where urTMS treatment is unsuccessful. Further large-scale studies are needed to explore its efficacy across diverse patient populations, stimulation parameters and to define its role in clinical practice.